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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EIn elderly or renally impaired volunteers, the antibody fragment idarucizumab rapidly and completely reversed the anticoagulation effect of dabigatran, sustained for at least 24 hours. Re-administration of dabigatran after 24 hours resulted in anticoagulation similar to that observed during initial treatment. There were no clinically relevant drug-related events; infusion-related effects were similar between arms.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Edabigatran antidote\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eanticoagulation\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ereversal\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group drug\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eidarucizumab\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Edabigatran\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003ESafety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 655075 and Establishment of BI 655075 Dose(s) Effective to Reverse Prolongation of Blood Coagulation Time by Dabigatran\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ENCT01955720\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EThe dabigatran antidote, idarucizumab, immediately and completely reversed anticoagulation by dabigatran in elderly and renally impaired volunteers, an effect that lasted for at least 24 hours. Joachim Stangier, PhD, Boehringer Ingelheim Pharma GmBH \u0026amp; Co KG, Biberach, Germany, presented data from the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BI 655075 and Establishment of BI 655075 Dose(s) Effective to Reverse Prolongation of Blood Coagulation Time by Dabigatran study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01955720\u0026amp;atom=%2Fspmdc%2F14%2F55%2F14.atom\u0022\u003ENCT01955720\u003C\/a\u003E].\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EIdarucizumab is the antigen-binding fragment of a humanized antibody that specifically targets dabigatran, a non-warfarin oral anticoagulant. Developed as an antidote to dabigatran, idarucizumab restored coagulation after easy and rapid intravenous administration. Key characteristics of idarucizumab are its initial short half-life of about 45 minutes and terminal half-life of 4.5 to 9 hours and that it is eliminated primarily renally through renal excretion and catabolism. A previous study in heathy male volunteers demonstrated that idarucizumab immediately and completely reversed the anticoagulation effect of dabigatran based on clotting times measured by diluted thrombin time (dTT), ecarin clotting time (ECT), activated partial thromboplastin time (aPTT), and thrombin time (TT) [Glund S et al. \u003Cem\u003ECirculation.\u003C\/em\u003E 2013]. The purpose of the current study was to further evaluate the effect of idarucizumab on anticoagulation reversal in elderly and renally impaired volunteers treated with dabigatran etexilate (DE).\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn this double-blind, randomized, 2-way crossover trial, 46 volunteers underwent 2 treatment periods, with a 6-day washout in between. During the first treatment period, patients received DE (220 mg, or 150 mg in the renally impaired) for 3 days, followed by a 5-minute infusion of idarucizumab or placebo about 2 hours after the last dose of dabigatran. A subset group of volunteers were re-treated with dabigatran 24 hours after the idarucizumab infusion. The study protocol was completed by all volunteers. The median peak dabigatran concentration was similar to that typically experienced by patients with atrial fibrillation.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EIn both age groups (45 to 64 and 65 to 80 years) and in patients with mild or moderate renal impairment, idarucizumab immediately reversed clotting times to baseline levels, as measured by dTT, ECT, aPTT, and TT, which was sustained for at least 24 hours (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). Anticoagulation was restored to initial levels when dabigatran was readministered 24 hours after the idarucizumab infusion.\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/55\/14\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of Idarucizumab on the Anticoagulation Effect of DabigatranDE, dabigatran etexilate; dTT, diluted thrombin time; RI, renal impairment (CLcr: mild RI \u0026#x2265;\u0026#x2009;60 to \u0026amp;lt;\u0026#x2009;90 mL\/min; moderate RI \u0026#x2265;\u0026#x2009;30 to \u0026amp;lt;\u0026#x2009;60 mL\/min); TT, thrombin time.Reproduced with permission from J Stangier, PhD.\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-291498083\u0022 data-figure-caption=\u0022Effect of Idarucizumab on the Anticoagulation Effect of DabigatranDE, dabigatran etexilate; dTT, diluted thrombin time; RI, renal impairment (CLcr: mild RI \u0026#x2265;\u0026#x2009;60 to \u0026amp;amp;lt;\u0026#x2009;90 mL\/min; moderate RI \u0026#x2265;\u0026#x2009;30 to \u0026amp;amp;lt;\u0026#x2009;60 mL\/min); TT, thrombin time.Reproduced with permission from J Stangier, PhD.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/55\/14\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/55\/14\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/55\/14\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/11638\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \u003Cp id=\u0022p-6\u0022 class=\u0022first-child\u0022\u003EEffect of Idarucizumab on the Anticoagulation Effect of Dabigatran\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EDE, dabigatran etexilate; dTT, diluted thrombin time; RI, renal impairment (CLcr: mild RI \u2265\u200960 to \u0026lt;\u200990 mL\/min; moderate RI \u2265\u200930 to \u0026lt;\u200960 mL\/min); TT, thrombin time.\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EReproduced with permission from J Stangier, PhD.\u003C\/p\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EThere were no clinically relevant drug-related adverse events in the study, and the rates of adverse events and local reactions were similar between the idarucizumab and placebo arms. In patients who received idarucizumab, there was a dose-dependent elevation in urine protein and low-weight proteins that returned to normal values within 24 hours.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EDr Stangier concluded that the data from this and other studies that have evaluated idarucizumab show that it is a specific antidote for anticoagulation caused by dabigatran and that it is well tolerated. In addition, the multicenter, phase 3 RE-VERSE AD trial [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT02104947\u0026amp;atom=%2Fspmdc%2F14%2F55%2F14.atom\u0022\u003ENCT02104947\u003C\/a\u003E] was initiated in May 2014 and will evaluate the efficacy and safety of dabigatran reversal by idarucizumab in patients who are taking dabigatran and present with a major bleeding event or require emergency surgery for other conditions.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/55\/14.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzm3c1\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm3c1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}